Is GP1BA p.Pro437Arg (c.1310C>G) pathogenic?

GP1BA p.Pro437Arg (c.1310C>G) is classified Uncertain significance in GP1BA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-21). AlphaMissense: likely benign (0.1547); Very rare (popmax 0.00533%, amr).

How common is GP1BA p.Pro437Arg (c.1310C>G) in the general population?

GP1BA p.Pro437Arg (c.1310C>G) is very rare (popmax 0.00533%, amr) (gnomAD).

What do computational predictors say about GP1BA p.Pro437Arg (c.1310C>G)?

AlphaMissense predicts likely benign (score 0.1547) — an in-silico prediction, not a clinical call.

GP1BA p.Pro437Arg

c.1310C>G · VCV3380460

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1547 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00533%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1547	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -12.45	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.42	GERP -0.99
Regional constraint	o/e 0.32	constrained · MANE · 135 bp · p 3.7e-07 · regional, not allelic
Overall
CADD	2.612	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00533% Admixed American · 1/18,752 alleles

Overall 0.000131% 1/763,276 alleles · very rare exomes 1/738,786 · genomes 0/24,490 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: GP1BA
Protein: p.Pro437Arg
Coding: c.1310C>G
MANE Select: NM_000173
Type: single nucleotide variant
Location: chr17:4933914 (GRCh38)
Gene constraint: LOEUF 1.289 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 64.65 · 22 PDB
Residue 437: the 'disordered' region

Full GP1BA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GP1BA p.Pro437= Benign ★★★ same residue
GP1BA p.Cys225Arg Likely pathogenic ★★★ same type
GP1BA p.Cys81Arg Pathogenic ★★★ same type
GP1BA p.Gln346Ter Likely pathogenic ★★★ same type
GP1BA p.Glu347Ter Likely pathogenic ★★★ same type
GP1BA p.Leu145Pro Likely pathogenic ★★★ same type
GP1BA p.Ser267Ter Likely pathogenic ★★★ same type
GP1BA p.Ser486Ter Likely pathogenic ★★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/gp1ba-p-pro437arg (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown